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首页> 外文期刊>Applied Microbiology and Biotechnology >An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain
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An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain

机译：使用糖多孢红霉菌mutB菌株的二甲基丙二酸二乙酯响应（Dmr）表型对红霉素工艺进行改进

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摘要

The Saccharopolyspora erythraea mutB knockout strain, FL2281, having a block in the methylmalonyl-CoA mutase reaction, was found to carry a diethyl methylmalonate-responsive (Dmr) phenotype in an oil-based fermentation medium. The Dmr phenotype confers the ability to increase erythromycin A (erythromycin) production from 250–300% when the oil-based medium is supplemented with 15 mM levels of this solvent. Lower concentrations of the solvent stimulated proportionately less erythromycin production, while higher concentrations had no additional benefit. Although the mutB strain is phenotypically a low-level erythromycin producer, diethyl methylmalonate supplementation allowed it to produce up to 30% more erythromycin than the wild-type (control) strain—a strain that does not show the Dmr phenotype. The Dmr phenotype represents a new class of strain improvement phenotype. A theory to explain the biochemical mechanism for the Dmr phenotype is proposed. Other phenotypes found to be associated with the mutB knockout were a growth defect and hyper-pigmentation, both of which were restored to normal by exposure to diethyl methylmalonate. Furthermore, mutB fermentations did not significantly metabolize soybean oil in the presence of diethyl methylmalonate. Finally, a novel method is proposed for the isolation of additional mutants with the Dmr phenotype.
机译：发现在甲基丙二酰-CoA突变酶反应中具有阻断作用的红细菌糖多孢菌mutB敲除菌株FL2281在油基发酵培养基中带有对丙二酸二乙酯的响应型（Dmr）。当在油基培养基中添加15 mM的这种溶剂时，Dmr表型赋予将红霉素A（红霉素）的产量从250-300％提高的能力。较低浓度的溶剂会相应地刺激减少红霉素的产生，而较高浓度则没有其他好处。尽管mutB菌株在表型上是低水平的红霉素生产者，但补充甲基丙二酸二乙酯可使它比野生型（对照）菌株（不显示Dmr表型的菌株）多生产30％的红霉素。 Dmr表型代表了一类新的菌株改良表型。提出了一种理论来解释Dmr表型的生化机制。发现与mutB基因敲除有关的其他表型是生长缺陷和色素沉着过度，通过暴露于甲基丙二酸二乙酯可将两者恢复正常。此外，在甲基丙二酸二乙酯存在下，mutB发酵不会显着代谢大豆油。最后，提出了一种新的方法来分离具有Dmr表型的其他突变体。

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